Emotional stress affects millions of people, and is a major health-related expense in the US. Despite great advances in our knowledge of the molecular, cellular and genetic factors that are involved, precious little is known about the effects of emotional stress on the neuronal circuits and ensembles that are the mediators between the cellular pathologies and the dysfunctional behavior. Recent advances have made it possible, for the first time, to record simultaneously from many neurons in one (or several) brain areas, and to apply new analysis methods to such data. These advances are now poised to produce new insights into the network's dynamical behavior. We propose to record simultaneously from many neurons in those parts of the mammalian brain that have been shown to be involved in emotional stress and drug addiction, which include the Ventral Tegmental Area (VTA), Prefrontal Cortex (PFC) and Nucleus Accumbens (NAc). The recordings will be carried out in mice that have been subjected to the behavioral protocol of social defeat (SD), which is used as an animal model for emotional stress, and which results in two distinct behavioral phenotypes, called resilient and susceptible. We shall compare the effect of SD on the dynamical behavior and interactions among the neural populations in these two behavioral phenotypes, to test the hypothesis that SD induces (or is at least correlated with) changes in the dynamical network properties of the mesolimbic system. This research differs from most of the previous work in this area in combining 3 crucial features: 1) It focuses not on individual neurons, but on the dynamical behavior and interactions within the relevant brain networks;2) It is related to the behavioral state of the animal, and 3) It will be carried out in vivo, rather than in vitro. It will therefore provide new information, not currently available, about the neuronal ensembles that occupy a critical intermediate brain level, between single neurons and whole animal behavior. It will thus shed new light on the brain mechanisms that are involved in emotional stress, and will provide new ways to assess the effectiveness of drugs. PUBLIC HEALTH RELEVANCE: We plan to use modern methods of network analysis to investigate the hypothesis that emotional stress is caused by changes in the dynamical behavior of neuronal groups in specific parts of the brain. After being exposed to aggressive behavior from other mice, some mice show signs of emotional stress, while others remain resilient. We shall compare the network properties of the stressed and resilient mice to discover how the emotional stress changes the group behavior of their neuronal ensembles.